Chinese Journal of Organic Chemistry >
Discovery and Structure-Activity Relationship Studies of Thiazole- Oxazole Tandem Heterocyclic RNA Splicing Inhibitors
Received date: 2022-02-25
Revised date: 2022-05-19
Online published: 2022-06-01
Precursor mRNAs (pre-mRNAs) undergo splicing to remove introns and ligation of their exons to yield mature mRNAs. Pre-mRNA splicing is an essential component of gene expression and proteomic diversity in higher organisms. However, the alternative splicing or mutation of splicing factors have been found in human diseases. By the use of the small molecules modulate the splicing process will provide potential treatment for related diseases. In this paper, circmcherry expression system was used to screen compounds that could affect splicing process. Several simple derivatives of natural product Leucamide A have been found to have inhibitory effects, and 36 compounds with thiazole-oxazole tadem structural core were designed and synthesized, of which methyl 2-((S)-1-(2-(2-((S)-1-(4-methoxybenzamido)-2-methylpropyl)thiazol-4- yl)-5-methyloxazole-4-carboxamido)ethyl)oxazole-4-carboxylate (9l) shows most potent inhibitory activity on splicing.
Rong Zhang , Xiang Gao , Lingling Chen , Fajun Nan . Discovery and Structure-Activity Relationship Studies of Thiazole- Oxazole Tandem Heterocyclic RNA Splicing Inhibitors[J]. Chinese Journal of Organic Chemistry, 2022 , 42(9) : 2925 -2939 . DOI: 10.6023/cjoc202202033
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